4LTS

Discovery of Potent and Efficacious Cyanoguanidine-containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	3DHF

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	8.6	292	0.2uL + 0.2uL drops containing 6mg/mL Nampt, 0.1M Sodium phosphate, 25-29% polyethylene glycol 3350, 0.2M NaCl, 1mM compound, pH 8.6, VAPOR DIFFUSION, HANGING DROP, temperature 292K

Crystal Properties
Matthews coefficient	Solvent content
2.34	47.38

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 60.782	α = 90
b = 106.314	β = 96.55
c = 82.94	γ = 90

Symmetry
Space Group	P 1 21 1

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	93	CCD	ADSC QUANTUM 315		2012-11-21	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ALS BEAMLINE 5.0.2	0.98400	ALS	5.0.2

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	Net I Over Average Sigma (I)	Redundancy	Number Reflections (All)	Number Reflections (Observed)	Observed Criterion Sigma (F)	Observed Criterion Sigma (I)	B (Isotropic) From Wilson Plot
1	1.7	50	99.8			115021	114791	2	2	19.76

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.7	1.76	99.9

Refinement

Statistics
Diffraction ID	Structure Solution Method	Starting model	Resolution (High)	Resolution (Low)	Cut-off Sigma (F)	Number Reflections (All)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (All)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	3DHF	1.692	46.416	1.34	115021	114746	5780	98.6	0.1895	0.1582	0.1566	0.1895	5% random

Temperature Factor Modeling
Anisotropic B[1][1]	Anisotropic B[1][2]	Anisotropic B[1][3]	Anisotropic B[2][2]	Anisotropic B[2][3]	Anisotropic B[3][3]
7.2006		-1.0048	10.0732		1.0533

RMS Deviations
Key	Refinement Restraint Deviation
f_dihedral_angle_d	12.953
f_angle_d	1.195
f_chiral_restr	0.082
f_bond_d	0.009
f_plane_restr	0.006

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	7548
Nucleic Acid Atoms
Solvent Atoms	1012
Heterogen Atoms	112

Software

Software
Software Name	Purpose
B3	data collection
PHASER	phasing
PHENIX	refinement
DENZO	data reduction
SCALEPACK	data scaling

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.